Proximity-dependent recruitment of Polycomb repressive complexes by the lncRNA Airn.

Proximity-dependent recruitment of Polycomb repressive complexes by the lncRNA Airn.
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DOI:
10.1016/j.celrep.2023.112803
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发表时间:
2023-07-25
期刊:
影响因子:
8.8
通讯作者:
--
中科院分区:
生物学1区
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--
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在小鼠胚胎发生期间,长非编码RNA(lncRNA)Airn的表达导致基因阻遏和Polycomb阻遏复合物(PRCs)在15-Mb结构域上不同程度的募集。其机制尚不清楚。使用高分辨率方法,我们在小鼠滋养层干细胞中表明,Airn表达诱导染色质结构的长期变化,这与PRC指导的修饰一致,并且以即使在没有Airn表达的情况下也与Airn基因座接触的CpG岛启动子为中心。Airn lncRNA和染色质之间的接触强度与PRC募集和PRC定向修饰的潜在强度相关。删除CpG岛接触的Airn基因座改变长距离抑制和PRC活动的方式,与染色质结构的变化。我们的数据表明,Airn表达招募PRCs到染色质的程度是由DNA调控元件控制的,这些元件调节Airn lncRNA产物与其靶DNA的接近度。Braceros等人绘制了DNA调控元件、Polycomb抑制复合物(PRCs)和lncRNA Airn之间的相互作用。他们发现Airn lncRNA和PRCs的存在在染色质上以锁定步骤相关,并且特定的DNA调控元件以不同的方式调节Airn的抑制强度。
During mouse embryogenesis, expression of the long non-coding RNA (lncRNA) Airn leads to gene repression and recruitment of Polycomb repressive complexes (PRCs) to varying extents over a 15-Mb domain. The mechanisms remain unclear. Using high-resolution approaches, we show in mouse trophoblast stem cells that Airn expression induces long-range changes to chromatin architecture that coincide with PRC-directed modifications and center around CpG island promoters that contact the Airn locus even in the absence of Airn expression. Intensity of contact between the Airn lncRNA and chromatin correlated with underlying intensity of PRC recruitment and PRC-directed modifications. Deletion of CpG islands that contact the Airn locus altered long-distance repression and PRC activity in a manner that correlated with changes in chromatin architecture. Our data imply that the extent to which Airn expression recruits PRCs to chromatin is controlled by DNA regulatory elements that modulate proximity of the Airn lncRNA product to its target DNA. Braceros et al. map interactions between DNA regulatory elements, Polycomb repressive complexes (PRCs), and the lncRNA Airn. They find that the presence of Airn lncRNA and PRCs correlates in lock-step on chromatin and that specific DNA regulatory elements modulate intensity of repression by Airn in different ways.
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